Smoking Cessation Pharmacotherapy Use in Pregnancy

Key Points Question How many pregnancies include use of prescription smoking cessation pharmacotherapies, especially during the first trimester? Findings In this cohort study of 1.7 million pregnancies in New South Wales, Australia; New Zealand; Norway; and Sweden from 2015 to 2020, use of varenicline and bupropion during pregnancy was low, while prescription nicotine replacement therapy was used during a larger proportion of pregnancies. For most pregnancies in which these medications were used, use occurred at least partly during the first trimester. Meaning These findings suggest that maternal use of smoking cessation pharmacotherapies aligns with current clinical recommendations; however, robust evidence on safety during pregnancy is needed.

admissions, outpatient consultations, and specialist consultations.Diagnoses are coded according to ICD-10 codes and surgical procedures coded according to Nordic Classification of Surgical Procedures. 5urther information about the data sources of the Nordic Pregnancy Drug Safety Studies collaboration are reported elsewhere. 3,4ntextual information regarding smoking cessation pharmacotherapies Government subsidy schemes for smoking cessation therapies vary between countries.
In Australia, bupropion (subsidised since 2001) and varenicline (subsidised since 2008) are prescription only.NRT products can be purchased over the counter or via prescription.Subsidy for NRT transdermal patches commenced from 2008 for Aboriginal and Torres Strait Islander people, followed by an extension to the general population from 2011. 9 NRT fast-acting formulations were PBS-listed since late 2019, 9 at the end of the period covered by PBS data available to this study.
In New Zealand, nicotine replacement therapies (NRT) such as patches, lozenges, and gums, bupropion and varenicline were subsidised from at least 2004 (exact date unknown), 2009 and 2010 respectively.Although NRT products can be purchased over the counter, discussions with New Zealand tobacco control experts, pharmacists and Pharmac (the New Zealand medication buying agency) suggest that most of the NRT obtained by individuals is likely to be via prescription and other sources captured by Pharmaceutical Collection data (author LP personal communications).
In Norway, varenicline is available through prescription only (reimbursed since 2007).NRT products are mostly available over the counter (since 2005), although preliminary analyses found small number of records of prescription NRT were filled during pregnancy.Bupropion is licensed for depression treatment only, the sustained-release bupropion (sold under brand name Zyban™) is indicated for smoking cessation.Zyban™ 150mg was marketed and dispensed (with the indication smoking cessation) from 2000 in Norway.
In Sweden, varenicline is available through prescription only (reimbursed since 2007).NRT patches and lozenges are available mostly over the counter (since 2006).Bupropion is licensed for depression treatment only, the sustained-release bupropion (sold under brand name Zyban™) is indicated for smoking cessation.
Table S2 shows the availability, recommended dosing, and recommended full course across the four jurisdictions, and calculation of days of supply for each dispensing item.In Australia, Norway and Sweden, medications are coded according to the ATC classification system while in New Zealand, the chemical ID (ChemID) is used.S2).
In order to define a course of treatment, we first selected all dispensing records that occurred between 200 days before DoC and date of childbirth.For each dispensing, we calculated days of supply based on amount dispensed and recommended daily dose (see supplemental Table S2).When there were multiple dispensing records, we summed up the days of supply, allowing for a 30-day gap between supply exhaustion and the subsequent dispensing.We considered a woman having another course of treatment when there was a gap >30 days between dispensings (see supplemental Figure 1).Only courses overlapping with the gestation period were included in the analyses.• Australia: based on the Australian Accessibility and Remoteness Index of Australia Plus, mapped to the area of maternal residence.There are five categories: major cities, inner regional, outer regional, remote and very remote.

FigureS1.
FigureS1.Determination of length of smoking cessation pharmacotherapy courses, start of bar indicates date of dispensing and the length of the bar represents the days of supply of the dispensing calculated based on recommended daily dose (TableS2).

Figure S2 .
Figure S2.Flow diagram of smoker re-classification algorithm based on the algorithm developed by Roper et al.PLOS ONE 2018.11Algorithm has been amended to account for pregnancies with multiple courses of smoking cessation pharmacotherapy which could be represented by both sides of the algorithm, addition of step 6 allows us to re-classify all pregnancies with at least one indication of smoking.
The NSW Perinatal Data Collection (July 2001 to December 2019) includes records for all live births and stillbirths of at least 20 weeks gestation or at least 400g birth weight delivered in NSW.Information on maternal characteristics, complications during pregnancy and delivery, and neonatal outcomes are recorded by the attending midwife or doctor.• The Pharmaceutical Benefits Scheme (PBS, January 2001 to December 2020) data include a record of every PBS listed medications dispensed to eligible individuals in community pharmacies and private hospitals.Information included PBS item number, generic name, anatomical therapeutic chemical (ATC) code, date of prescribing, date of supply, quantity, and patient beneficiary status (social security or general).Mediations purchased over the counter and those administered in public hospitals are not included.• The Admitted Patient Data Collection (July 2001 to June 2020) includes a record for every public and The Programme for the Integration of Mental Health Data (July 2008 -December 2021) is the national mental health and addiction information collection of service activity and outcomes data for health consumers.Further details about the New Zealand pregnancy cohort are reported elsewhere.
1rivate hospital separation in NSW.Information includes patient demographics, diagnoses, procedures, and external causes of injuries.Diagnoses are coded according to the International Statistical Classification of Diseases and Related Problems, 10th revision -Australian Modification (ICD-10-AM) while procedures are coded according to the Australian Classification of Health Interventions (ACHI).More details regarding the NSW linked data are reported elsewhere.1

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7he Medical Birth Registry of Norway (January 2004 to December 2020) is a mandatory registration of all live-and stillbirths and pregnancies of at least 12 weeks of gestation.The register contains information about pre-pregnancy maternal health, complications during pregnancy or birth, neonatal outcomes, infant diagnoses, or evidence of congenital abnormalities.It also contains data about miscarriages and pregnancy termination for fetal anomaly.7•The Norwegian Prescription Database (January 2004 to December 2020) is a mandatory registration of all medications dispensed in pharmacies in Norway.Information includes ATC codes, medication strength, defined daily doses in a package, package size and dispensing date.Medications that are purchased over the counter or supplied to hospitals and nursing homes are not included.Since March 2009, indication for reimbursement was coded according to ICD-10 codes and version 2 of the International Classification of Primary Care. 4 • The Norwegian Patient Registry (January 2008 to December 2020) is a nationwide registry covering all hospital admissions, outpatient consultations, and specialist consultations.Diagnoses (primary and several secondary diagnoses) are coded according to the ICD-10 codes since 2008.8 Sweden • The Swedish Medical Birth Register (January 2005 to December 2019) covers all live-and stillbirths of at least ≥ 22 weeks gestation (gestation ≥28 weeks before 2008).Information included pre-pregnancy maternal health, complications during pregnancy or birth, neonatal outcomes, and infant diagnoses.6 • The Swedish Prescribed Drug Register (January 2005 to December 2019) contains complete national data on all prescription pharmaceuticals dispensed.Dispensing records contain ATC codes, date of dispensing, the dose, and quantity.Hospital administered medications, vaccines and over the counter medications are not included. 4 The Swedish National Patient Register (January 2005 to December 2019) covers all hospital

Table S2 . Availability and recommended dosing of smoking cessation pharmacotherapies across four countries and days of supply calculation.
© 2024 Robijn AL et al.JAMA Network Open.© 2024 Robijn AL et al.JAMA Network Open.

Table S4 . Definitions of maternal characteristics Maternal characteristics Jurisdiction-specific definition
Aboriginal and/or Torres Strait Islander status recorded in the most recent perinatal record; if missing supplemented by information recorded in the corresponding delivery hospital admission record • New Zealand: Māori ethnicity ever recorded in perinatal, hospital admission, mortality, National Health Index or pharmaceutical dispensing records.• Norway and Sweden: Not applicable Country of birth • Australia: Country of birth recorded in the most recent perinatal record, if missing, supplemented by information recorded in the hospital admission corresponding to the childbirth delivery • New Zealand: Not available • Norway/Sweden: As recorded in MBR or population register Socio-economic disadvantage of residential area • Australia: Geocoded statistical area, recorded in hospital delivery admission and mapped to ABS 2016 Census, SEIFA Relative Socio-economic Disadvantage (IRSD) • New Zealand: The NZ Index of Deprivation (NZDep) • Norway/Sweden: not available Remoteness of residence

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New Zealand: based on the Geographical Classification for Health which is similar to the Australian Accessibility and Remoteness Index of Australia Plus.There are five categories: Urban 1, Urban 2, Rural 1, Rural 2, and Rural 3 • Norway/Sweden: not available Body Mass Index (BMI) in early pregnancy• Australia: weight and height measures available since 2016, may contain missing data • New Zealand: BMI is recorded in the National Maternity Collection (some missing data) • Norway/Sweden: As recorded in MBR or calculated from maternal weight and height at first antenatal visit.